Nanney L B, Sundberg J P, King L E
Department of Plastic Surgery, Vanderbilt School of Medicine, Nashville, Tennessee, USA.
J Invest Dermatol. 1996 Jun;106(6):1169-74. doi: 10.1111/1523-1747.ep12347791.
Epidermal growth factor receptors (EGF-Rs) are elevated in active human psoriatic lesions, but decrease in resolving lesions. Similar biologic responses in EGF-R levels have been demonstrated within human psoriatic skin grafted onto mice. We tested the hypothesis that flaky-skin mice (fsn/fsn), one proposed genetic animal model of psoriasis, would display EGF-R levels comparable to human psoriatic epidermis and show similar biologic responses. EGF-R levels were characterized in unperturbed sites in fsn/fsn skin and +/? skin by enzyme-linked immunosorbent assay, 125I-EGF binding, and immunostaining. Altered EGF-R levels were noted after mild trauma (tape stripping) or under resolving conditions (30 doses of 50 mJ/CM2 ultraviolet B, 2.5 mg/kg oral cyclosporin A, or daily 30 microg/ml topical EGF). Increased EGF-R immunostaining was observed in involved flaky epidermal sites before treatment. To determine whether a hyperproliferative (Koebner) reaction could be induced, we tape stripped fsn/fsn tail and non-flaky dorsal sites. EGF-R levels in dorsal epidermis increased by days 3-4 after injury by enzyme-linked immunoabsorbent assay methods. When fsn/fsn mice received one of three different treatments for 6 weeks, the skin returned to a normal phenotype both grossly and microscopically. Immunoreactive EGF-R in treated, but not untreated, sites decreased to either normal or nondetectable levels. These data indicate that fsn/fsn mice exhibit an EGF-R profile identical to that of lesional and nonlesional human psoriatic epidermis. Modulations of the flaky phenotype in response to injury and three different treatments suggest that fsn/fsn is a useful in vivo model for examining new treatment modalities for psoriasiform skin diseases.
表皮生长因子受体（EGF-Rs）在活动性人类银屑病皮损中升高，但在皮损消退时降低。在移植到小鼠身上的人类银屑病皮肤中也证实了EGF-R水平存在类似的生物学反应。我们检验了这样一个假设：片状皮肤小鼠（fsn/fsn），一种被提出的银屑病基因动物模型，其EGF-R水平与人类银屑病表皮相当，并表现出类似的生物学反应。通过酶联免疫吸附测定、¹²⁵I-EGF结合和免疫染色，对fsn/fsn皮肤和+/?皮肤未受干扰部位的EGF-R水平进行了表征。在轻度创伤（胶带剥离）或消退条件下（30次剂量为50 mJ/cm²的紫外线B、2.5 mg/kg口服环孢素A或每日30 μg/ml局部应用EGF）后，观察到EGF-R水平发生改变。在治疗前，在受累的片状表皮部位观察到EGF-R免疫染色增加。为了确定是否能诱导出增生性（科布纳）反应，我们对fsn/fsn小鼠的尾巴和非片状背部皮肤进行胶带剥离。通过酶联免疫吸附测定法，背部表皮的EGF-R水平在受伤后第3至4天升高。当fsn/fsn小鼠接受三种不同治疗之一6周后，皮肤在大体和显微镜下均恢复到正常表型。经治疗部位（而非未治疗部位）的免疫反应性EGF-R降至正常或不可检测水平。这些数据表明，fsn/fsn小鼠表现出与人类银屑病皮损和非皮损表皮相同的EGF-R谱。对损伤和三种不同治疗的片状表型调节表明，fsn/fsn是一种用于研究银屑病样皮肤病新治疗方法的有用体内模型。
